1. Field of the Invention
The present invention relates to methods of diagnosing and treating cancer, and particularly to a method for determining risk of metastatic relapse in a patient diagnosed with colorectal cancer by screening colorectal cancer patients for aberrant levels of at least one of 42 genes identified as markers of likely metastatic occurrence, and subsequently treating the patient.
2. Description of the Related Art
Colorectal cancer (CRC) is one of the most common cancers in the world. Early detection and surgery with excision of the tumor is currently of critical importance for a successful treatment. For localized tumors, i.e. tumors that have not evolved into a metastasizing disease, surgical intervention with radical resection of the tumor and surrounding bowel and tissues is performed. Colorectal tumors are categorized into several stages according to Dukes' stages A-D or more recently according to the TNM classification. Early stage tumors (Dukes' stages A and B) are generally associated with a relatively favorable outcome, while later stage tumors, presenting with metastasis (Dukes' stage C and D) have poor survival rates. Unfortunately, metastasis often goes undetected until the tumor has grown to a considerable size. The tumor typically metastasizes to regional lymph nodes, but distant metastasis to the liver and lung are also common.
Patients with early-stage CRC (Stage I and II or Dukes' A and B) undergo surgical resection only and are not treated chemotherapeutically. Almost one fourth of early stage patients with non-metastatic disease, however, relapse with metastasis later, Patients diagnosed with metastatic forms of CRC, namely stages Dukes' C with lymph node metastasis and Dukes' D with hematological dissemination, have five year survival rates of 37% and 11%, respectively. Patients diagnosed at an early stage (Dukes' A and B) with no evidence of metastatic disease at time of surgery have a significantly better prognosis featuring five-year survival rates of 85% and 67%, respectively (Cancer Research UK, 2004). However, a significant proportion of these patients (10-45%) relapse with metastatic disease.
Chemotherapy has proven effective for Dukes' C stage tumors. Newer studies also indicate the value of chemotherapy for some patients with early colorectal cancer at risk of metastatic relapse. However, although chemotherapeutic intervention has been implemented for some patients with early colon cancer, its implementation as a routine treatment is not cost effective and can be counterproductive. The side effects associated with the treatment, in particular, make it desirable to avoid application of chemotherapy except in cases of high relapse risk.
Identifying patients at high risk of metastatic relapse from CRC would be useful to target treatment to only those patients, and thereby avoid overtreatment. Suitable markers for identifying this population are currently lacking.
Thus, a method for determining risk of metastatic relapse in a patient diagnosed with colorectal cancer solving the aforementioned problems is desired.